The project investigates a range of nutritional and related factors, concentrating on the role of vitamins E, D and other micronutrients, energy balance, insulin and growth factors, hormones, and genetic factors within several projects, including the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, the NCI Breast and Prostate Cancer Cohort Consortium (BPC3), the Selenium and Vitamin E Cancer Prevention Trial (SELECT), the NIH-American Association of Retired Persons (AARP) Study, the Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) Trial, and the Biology of the Prostate Cancer Prevention Trial (PCPT) Project. Some of these involve consortium approaches to discovering genetic determinants of prostate cancer that have contributed to our knowledge of this malignancy and some hypothesized biological pathways. The genes are being evaluated as candidates and through GWAS, including of circulating nutrient phenotypes (a new area of discovery that is providing useful leads with respect to prostate and other cancers). Circulating insulin-like growth factors and insulin have been studied, with strong etiologic associations found, whereas higher androgen status was shown to not be an important risk factor. New prostate case-control data in the ATBC Study showed a strong positive 25OH-vitamin D-prostate cancer association, and vitamin D metabolizing and signaling genes and testing gene-nutrient interactions are being examined.